Although asthma is a major public health problem in Puerto Ricans, little is known about the relative contribution of genetic and environmental factors to the development and severity of asthma in this ethnic minority group. This application will examine the relation between selected genetic and environmental factors and asthma in Puerto Rican children. To this end, we will recruit 500 Puerto Rican children with asthma (cases) and 500 Puerto Rican children without asthma (controls) in Hartford, Connecticut. To begin to identify genetic factors influencing asthma in Puerto Ricans, we will genotype single nucleotide polymorphisms (SNPs) in 20 genes that control the development and regulation of T-helper (Th)1 cells, Th2 cells, and regulatory T cells (Tregs) and may therefore influence the pathogenesis and severity of asthma in Puerto Ricans. We will then test for association between SNPs and haplotypes in these candidate genes and a) asthma (in all subjects), b) lung function phenotypes (airway responsiveness, spirometric measures of airflow obstruction [FEV1 and FEV1/FVC], and bronchodilator response) and atopy phenotypes (serum total and allergen-specific IgE, skin test reactivity to allergens, and peripheral blood eosinophil count) separately in cases and in controls, and c) asthma severity in cases. To examine the relation between indoor allergen exposure and asthma phenotypes in Puerto Ricans, we will assess exposure to pets in early life (during pregnancy and/or the first year of life) by parental report and measure the levels of six allergens (dust mite, cockroach, cat, dog, rat, and mouse) in the households of participating children. We will then examine whether parental report of exposure to each of two pets (dogs and cats) in early life is associated with reduced risks of asthma (in all subjects) and atopy (separately in cases and in controls). In addition, we will examine whether current exposure to high levels of indoor allergens (dust mite, cockroach, dog, cat, rat, and mouse) is associated with asthma severity and lung function phenotypes (reduced FEV1 and FEV1/VFVC, increased airway responsiveness, and reduced bronchodilator responsiveness) in cases, and with atopy phenotypes (e.g., increased serum total IgE) in cases and in controls. We will then examine whether SNPs and/or haplotypes in genes associated with asthma/asthma phenotypes interact with parental report of pet exposure in early life and/or current exposure to indoor allergens in influencing asthma and intermediate phenotypes of asthma (asthma severity, lung function phenotypes, and atopy phenotypes) in Puerto Rican children. By conducting a population-based case-control association study with adequate sample size in Puerto Rican children, we will start to address a significant yet unstudied problem: the influence of genetic and environmental factors on the development and severity of asthma in Puerto Ricans. This application will contribute greatly to our understanding of asthma in general, and among Puerto Ricans in particular.